Stable Mn(III) porphyrins mimic superoxide dismutase in vitro and substitute for it in vivo.
Year: 1994
Type: article
Abstract: Several manganic porphyrins, with substituents on the methine bridge carbons, were prepared and examined for stability, redox behavior, catalysis of the dismutation of superoxide radical (O;), and the ability to protect a superoxide dismutase (SOD)-null strain of E. coli against dissolved oxygen and a SOD-competent strain against paraquat.All of the compounds tested exhibited reversible redox behavior and were stable to EDTA in both the oxidized and reduced states, and several were able to catalyze the dismutation of 0; with the rate constants of "10' M -~ s-'.The marked protective effects of some of these compounds exceeded that which could be anticipated on the basis of such rate constants.The tetrakis (1-methyl-4-pyridyl) compound was reduced enzymatically at the expense of NADPH and nonenzymatically by GSH and was kept in the reduced state within E. coli.Since the rate constant for reoxidation of the reduced form by 0; is 4 x lo9 M-' s-', it appears that this compound acts in vivo as an NADPWGSHO; oxidoreductase rather than as an SOD mimic.Its ability to facilitate aerobic growth of the SOD-null strain can be explained on this basis.Superoxide radical (Oil, generated during both spontaneous and enzyme-catalyzed oxidations, is catalytically scavenged by SODS'; which, by so doing, provide an important defense (1,2).O;, if not removed by SOD, can initiate free radical chain oxidations of low molecular weight reductants (3-81, inactivate enzymes (9-12, 14, 151, and give rise to very reactive hydroxyl or alkoxy1 radicals through iron-or copper-catalyzed interactions with HOOH or ROOH (16-21).0; can also react, at diffusion-limited rate, with NO, yielding peroxynitrite (22).It is reasonable, therefore, that 0, should be a participant in a variety of physiological and pathological processes.The ability of SOD to ameliorate reperfusion injury (23-27), inflammations (28-30), multiorgan failure (31), brain trauma (32), and other conditions (33, 34) indicates that this is the case.It is *
Source: Journal of Biological Chemistry
Authors: K.M. Faulkner, S.I. Liochev, I. Fridovich
Institution: Duke Medical Center
Language: English
Subfield: Inorganic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W1533259206